Conjugation of an Antisense Oligodeoxynucleotide to Ribonuclease H Results in Sequence-Specific Cleavage and Intracellular Inhibition of HCV Gene Expression

2003 ◽  
Vol 14 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Toshiko Fukuma ◽  
Cherie M. Walton ◽  
Catherine H. Wu ◽  
George Y. Wu
Keyword(s):  
Gene Expression ◽  
Ribonuclease H ◽  
Antisense Oligodeoxynucleotide ◽  
Intracellular Inhibition

Intracellular Inhibition of Hepatitis B Virus S Gene Expression by Chimeric DNA-RNA Phosphorothioate Minimized Ribozyme

2002 ◽  
Vol 12 (4) ◽  
pp. 257-264 ◽  
Author(s):  
Theresa May Chin Tan ◽  
Lei Zhou ◽  
Sandrine Houssais ◽  
Bee Leng Seet ◽  
Stephan Jaenicke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
S Gene ◽  
B Virus ◽  
Intracellular Inhibition

Transcript of protein kinase A knock-down modulates feeding behavior and neuropeptide Y gene expression in phenylpropanolamine-treated rats

2007 ◽  
Vol 31 (2) ◽  
pp. 306-314 ◽  
Author(s):  
Yih-Shou Hsieh ◽  
Shun-Fa Yang ◽  
Shu-Chen Chu ◽  
Dong-Yih Kuo
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Neuropeptide Y ◽  
Protein Kinase A ◽  
Mrna Level ◽  
Camp Response Element Binding ◽  
Antisense Oligodeoxynucleotide ◽  
Mrna Levels ◽  
Knock Down ◽  
Kinase A

Neuropeptide Y (NPY) is an appetite-controlling neuromodulator that contributes to the appetite-suppressing effect of phenylpropanolamine (PPA). Aims of this study were to investigate whether protein kinase A (PKA) signaling is involved in regulating NPY gene expression and PPA-induced anorexia. Rats were given daily with PPA for 5 days. Changes in daily food intake and hypothalamic NPY, PKA, cAMP response element binding protein (CREB), and pro-opiomelanocortin (POMC) gene expression were measured and compared. To further determine if PKA was involved, intracerebroventricular infusions of antisense oligodeoxynucleotide were performed at 60 min before daily PPA treatment in freely moving rats. Results showed that daily PKA, CREB, and POMC expression were increased following PPA treatment, which showed a closely reverse relationship with alterations of decreased feeding behaviors and NPY mRNA levels. Results also showed that PKA knock-down could block PPA-induced anorexia as well as restore NPY mRNA level, indicating the involvement of PKA signaling in the regulation of NPY gene expression. It is suggested that hypothalamic PKA signaling may participate in the central regulation of PPA-mediated appetite suppression via the modulation of hypothalamic NPY gene expression. The present findings reveal that manipulations at the molecular level of PKA or cAMP may allow the development of therapeutic agents to improve the undesirable properties of PPA or other amphetamine-like anorectic drugs.

Uncoordinated Inhibition of Gene Expression for Muscle Proteins by a Troponin T Antisense Oligodeoxynucleotide

1998 ◽  
Vol 8 (3) ◽  
pp. 237-247 ◽  
Author(s):  
JOHANNA OJALA ◽  
MONIDEEPA CHOUDHURY ◽  
JNANANKUR BAG
Keyword(s):  
Gene Expression ◽  
Troponin T ◽  
Antisense Oligodeoxynucleotide ◽  
Muscle Proteins

scholarly journals Antisense Oligodeoxynucleotide Perfusion Blocks Gene Expression of Synaptic Plasticity-Related Proteins Without Inducing Compensation in Hippocampal Slices

BIO-PROTOCOL ◽  
2019 ◽  
Vol 9 (19) ◽  
Author(s):  
Panayiotis Tsokas ◽  
Bruno Rivard ◽  
Changchi Hsieh ◽  
James Cottrell ◽  
André Fenton ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Hippocampal Slices ◽  
Antisense Oligodeoxynucleotide ◽  
Related Proteins

Antisense Oligodeoxynucleotide Inhibition of HIV Gene Expression

1989 ◽  
Author(s):  
Eric Wickstrom
Keyword(s):  
Gene Expression ◽  
Antisense Oligodeoxynucleotide

Antisense Oligodeoxynucleotide Technology: Potential Use for the Treatment of Malignant Brain Tumors

1998 ◽  
Vol 5 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Herbert H. Engelhard
Keyword(s):  
Gene Expression ◽  
Brain Tumors ◽  
Relevant Information ◽  
In Vivo Studies ◽  
Antisense Oligodeoxynucleotide ◽  
Malignant Brain Tumors ◽  
Antisense Odns ◽  
The Brain

Background: Antisense oligodeoxynucleotides (ODNs) have been proposed as a new therapy for patients with cancer, including malignant brain tumors. Antisense ODNs are taken up by tumor cells and selectively block gene expression. Use of ODNs for brain tumors is attractive due to their theoretical specificity, relative ease of production and, to date, paucity of reported adverse effects. This article presents current information regarding antisense ODNs and their possible future use for the treatment of brain tumors. Methods: The available published experimental and clinical information regarding antisense ODN treatment of glioblastoma cells and administration into the central nervous system (CNS) was reviewed. Other clinically relevant information pertaining to the molecular biology of antisense ODNs was also collected and summarized. Results: Targets for antisense ODN therapy in malignant glioma cells have included c-myc, c-myb, c-sis, c-erb B, CD44, p34cdc2, bFGF, PDGF, TGF-beta, IGF-1, PKC-alpha tumor necrosis factor, urokinase, and S100beta protein. Few in vivo studies of ODN treatment of brain tumors have yet been reported. Systemically administered ODNs enter the brain only in extremely small quantities; therefore, microinfusion into the brain has been recommended. Conclusions: Antisense ODNs have been used successfully to block glioblastoma gene expression in vitro and expression of multiple genes within the CNS of experimental animals. Upcoming clinical trials will address the safety of antisense ODN use against malignant brain tumors.

scholarly journals Suppression of .ALPHA.-amylase gene expression by antisense oligodeoxynucleotide in barley cultured aleurone layers.

1992 ◽  
Vol 67 (2) ◽  
pp. 147-154 ◽  
Author(s):  
Nobuhiko TSUTSUMI ◽  
Keiko KANAYAMA ◽  
Shigemitsu TANO
Keyword(s):  
Gene Expression ◽  
Alpha Amylase ◽  
Antisense Oligodeoxynucleotide ◽  
Amylase Gene ◽  
Alpha Amylase Gene

Phase I Clinical/Pharmacokinetic and Pharmacodynamic Trial of the c-raf-1 Antisense Oligonucleotide ISIS 5132 (CGP 69846A)

1999 ◽  
Vol 17 (7) ◽  
pp. 2227-2227 ◽  
Author(s):  
James P. Stevenson ◽  
Kang-Shen Yao ◽  
Maryann Gallagher ◽  
David Friedland ◽  
Edith P. Mitchell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Mononuclear Cells ◽  
Maximum Tolerated Dose ◽  
Mitogen Activated Protein Kinase ◽  
Antisense Oligodeoxynucleotide ◽  
Oncogenic Signaling ◽  
Time Curve ◽  
Peripheral Blood Mononuclear ◽  
Mitogen Activated Protein

PURPOSE: Raf-1 is a protein kinase that plays a broad role in oncogenic signaling and acts as a downstream effector of Ras in the mitogen-activated protein kinase pathway. The present study was designed to determine the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetics, and antitumor activity of the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A; ISIS Pharmaceuticals Inc, Carlsbad, CA). The effect of ISIS 5132 on c-raf-1 gene expression in peripheral-blood mononuclear cells (PBMCs) of treated patients was studied using a reverse transcriptase polymerase chain reaction assay. PATIENTS AND METHODS: Patients with refractory malignancies received ISIS 5132 as a 2-hour intravenous infusion three times weekly for 3 consecutive weeks. Pharmacokinetic sampling was performed during the first cycle in all patients; PBMCs for c-raf-1 mRNA analysis were collected at baseline and on days 3, 5, 8, and 15 of cycle 1 and on day 1 of each cycle thereafter. RESULTS: Thirty-one patients received ISIS 5132 at one of nine dose levels ranging from 0.5 mg/kg to 6.0 mg/kg. Clinical toxicities included fever and fatigue, but these were not dose limiting. A clinically defined MTD was not reached. The harmonic mean half-life of ISIS 5132 was 59.8 minutes (range, 35.5 to 107.3 minutes). The area under the concentration-time curve increased linearly with dose, and mean plasma clearance was 1.86 mL/kg/min (range, 1.21 to 2.41 mL/kg/min). Two patients experienced prolonged stable disease lasting more than 7 months, which was associated with persistent reduction in c-raf-1 expression in PBMCs. Significant decreases in c-raf-1 expression were identified at time points after the baseline value (P < .05) at doses ≥ 2.5 mg/kg. CONCLUSION: ISIS 5132 is well tolerated at doses up to 6.0 mg/kg when administered as a thrice weekly 2-hour infusion for 3 consecutive weeks. The pharmacokinetic behavior of the drug is reproducible, and suppression of target gene expression is observed in circulating PBMCs.

Sign in / Sign up

Export Citation Format

Share Document